The Tri-Institutional MD-PhD Program is a joint undertaking by Weill Medical College of Cornell University (WCMC), The Rockefeller University (RU), and the Sloan-Kettering Institute (SKI) to train biomedical investigators who have advanced understanding of biomedical science and mastery of contemporary research skills, and yet are grounded in human biology, pathobiology and clinical medicine, and thus are equipped to transfer advances in basic research to the understanding, prevention, and treatment of human disease. The three institutions operate two graduate schools, Cornell University Graduate School of Medical Sciences (WGS, a joint undertaking between WCMC and SKI) and RU; the Tri-Institutional MD-PhD Program was formed in 1991, when two independent MD-PhD Programs operated by the three institutions, the WCMC-RU Program and the WCMC-WGS Program, were joined to form the present program. The present application requests funds to continue MD-PhD training at the three institutions beyond the 30th year (the predecessor WCMC-RU Program was formed in 1972; it has had NIH funding since 1974). MSTP trainees complete all the requirements for the MD degree at WCMC. They get their PhD training in the research laboratories in three research institutions, and receive their degree from either RU or WGS. The Tri-Institutional MD-PhD Program brings together faculty in -250 independent research laboratories. More than 200 MD-PhDs have graduated from the Tri-Institutional MD-PhD Program and its predecessors; currently there are 99 students in the Program. The current trainees come from 32 undergraduate schools, with more than 50% coming from six schools (Harvard, Yale, Princeton, Stanford, Brown, and Cornell). The average GPA is 3.74 and the combined MCAT score is 36. Accepted trainees arrive in early July before the start of the medical school education. During the first two years in the program they complete their medical school coursework, they take additional graduate level courses designed specifically for MD-PhD students, and they complete three research rotations, in three different laboratories, before they settle into their thesis laboratory. When the students choose a research laboratory, they enroll in the graduate school with which their thesis mentor is associated. The students must satisfy the specific thesis requirements of their graduate school, but they can cross register and take courses for credit in the other graduate school. At the end of their research training, after they have defended their thesis, the students return to complete their clinical training at WCMC. The quality of the training provided by the Program can be judged by the fact that 80% of the graduates of the predecessor programs are now in full-time academic positions.